INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Kaipei Luo,Shaoping Yin,Ruixia Zhang,Hua Yu,Guangji Wang,Juan Li
The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase . mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro . More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo , with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.
研究领域:
肿瘤学
·
纳米医学
·
药剂学
·
分子靶向治疗
·
药物递送系统
·
转化医学
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Bo Li,Shigang Pang,Xinxin Li,Yanhai Li
Here we demonstrate a type of pH and redox dual-responsive micelles, which were self-assembled in aqueous solution by an amphiphilic polymer, methoxypoly(ethylene glycol)-cystamine-poly(L-glutamic acid)-imidazole (mPEG-SS-PGA-IM). Considering tumor cells or tissues exhibiting low pH values and high glutathione (GSH) concentration, mPEG-SS-PGA-IM micelles possessed the charge conversion at pH of tumor tissues, which can facilitate cellular uptake of tumor cells. Furthermore, mPEG-SS-PGA-IM micelles can escape from endo/lysosomes based on the proton sponge effect, following degraded by higher concentration of GSH in cytoplasm. CLSM images of HCT116 cells indicated that mPEG-SS-PGA-IM micelles can escape from endo/lysosomes and enter cytoplasm. MTT assay showed that (paclitaxel) PTX-loaded mPEG-SS-PGA-IM micelles had higher cytotoxicity against HCT116 cells compared with PTX-loaded mPEG-PBLG and mPEG-SS-PBLG micelles. These results indicated that these mPEG-SS-PGA-IM micelles, as novel and effective pH- and redox-responsive nanocarriers, have great potential to both improve drug targeting efficiency while also enhancing the antitumor efficacy of PTX.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Xiaodan Wu,Jingsong Cao,Sansan Bao,Guansong Shao,Zihan Wang,Bingyang Qin,Tao Wang,Yujie Fu
In this article, we successfully prepared three-dimensional cellulose microspheres modified by molecularly imprinted polymer for paclitaxel recognition and separation (3D-CM &PTX&MIPs). The material was characterized by Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), Thermogravimetric Analysis (TG) and diffraction of X-rays (XRD). Under the optimized adsorption conditions, the maximum adsorption capacity reached 65.7 mg/g. And after 5 runs of reuse, (3D-CM&PTX&MIPs) still maintained a reusability rate of 90%. Besides, (3D-CM&PTX&MIPs) showed excellent selectivity for target PTX. Finally, (3D-CM&PTX&MIPs) was used for PTX recognition and separation in the extracts of yew leaves. This research laid a good foundation and scientific basis for the efficient, environmentally friendly, and rapid enrichment of metabolites in plants using bio-based molecularly imprinted polymers.
研究领域:
材料科学
·
药物化学
·
植物代谢研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Colloid and Interface Science Communications
·
2020
·
IF 2.831
Yue Ke,Lele Cui,Zhifang Ma,Xiaodong Xu,Runhai Chen,Xiaohui Lan,Qiang Shi,Jinghua Yin
Although heparin-based nanoparticles are widely used to treat cancer, the knowledge on the effect of heparin derivative and heparin-based nanoparticles on cancer-associated thrombosis is still lacking. To address this issue, the heparin derivatives including amphiphilic heparin-deoxycholic acid (DOCA) polymer with non-sensitive (Hep-DOCA) and redox-sensitive properties (Hep-ss-DOCA) are synthesized, and paclitaxel (PTX) is encapsulated in heparin-based micelles to fabricate nanoparticles. The chemical structure of synthesized polymer, the size, morphology and stability of nanoparticles and redox-sensitivity of nanoparticles are analyzed. And the effect of heparin-deoxycholic acid polymer and PTX loaded nanoparticles on cancer-associated thrombosis are investigated both in vitro and in vivo. It is found that redox-sensitive PTX/nanoparticles is effectively in reducing thrombosis for cancer mice. This result is mainly attributed to down-regulation for coagulation after apoptosis of cancer cell. This work not only clarifies the effect of heparin-based nanoparticles on blood hypercoagulation but provides basic principles to inhibit cancer-associated thrombosis.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
血液学
✓ 已验证
产品关联
DOI
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2014
·
IF 3.209
Erxi Che,Yikun Gao,Long Wan,Ying Zhang,Ning Han,Junling Bai,Jia Li,Zhou Sha,Siling Wang
We reported a magnetic targeted drug delivery system based on core/shell structural magnetic mesoporous silica nanoparticles (MMSNs) and the surface of MMSNs was coated by gelatin layer. In this system, the gelatin layer retarded the diffusion of paclitaxel (PTX, model drug) from quickly moving into the bulk solution to achieve sustained release of PTX. In addition, glutaraldehyde (GA) was used as crosslinking agent to crosslink the coating layer and the release of PTX could be regulated by adjusting the degree of crosslinking of the gelatin layer. The gelatin coated MMSNs (MMSN@GELs) had a saturated magnetization of 5.53 emu/g and could facilely response to an external magnet. To confirm our hypothesis that the carriers could be guided by an external magnetic field in vivo, the ex vivo imaging study and quantitative analysis were conducted. The results reflected that the external magnet altered the biodistribution of the magnetic carriers, so that more magnetic carriers were found to accumulate in tumors rather than to accumulate in normal tissues. Moreover, tumor reduction study reflected that the tumor growth of the group treated with PTX/MMSN@GELs in the presence of an external magnetic field were significantly delayed without an obvious body weight loss compared with PTX/MMSN@GELs in the absence of the magnet and with the commercial Taxol® at the same dose. All the results suggested that MMSNs coated by gelatin would be promising drug carriers for effective delivery of chemotherapeutic agents.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Feiyang Deng,Hua Zhang,Xing Wang,Yuan Zhang,Hongxiang Hu,Siyang Song,Wenbing Dai,Bing He,Ying Zheng,Xueqing Wang,Qiang Zhang
Drug nanocrystals (NCs) appear to be favorable to improving oral bioavailability of poorly water-soluble drugs as evidenced by the great success they have had in the market. However, the pathway and mechanism of drug NCs through epithelial membrane are still unclear. In an attempt to clarify their transport features, paclitaxel nanocrystals (PTX-NCs), and paclitaxel hybrid NCs with lipophilic carbocyanine dyes, were prepared and characterized as the models. The endocytosis, intracellular trafficking, paracellular transport, and transcytosis of PTX-NCs were carefully investigated with Förster resonance energy transfer (FRET) analysis, as well as a colocalization assay, flow cytometry, gene silencing, Western-blot, transepithelial electrical resistance (TEER) study and other approaches on MDCK cells. It was found that rod-like PTX-NCs could transport through the monolayer intact, and the process of endocytosis proved to be time and energy dependent. Endoplasmic reticulum (ER) and Golgi complexes were colocalized with PTX-NCs in cells, so the ER–Golgi complexes/Golgi complexes–basolateral membrane pathway may be involved in the intracellular trafficking and transcytosis of PTX-NCs. It was demonstrated here that cav-1, dynamin, and actin filament modulated the endocytosis process, and Cdc 42 regulated the transcytosis process. In addition, no paracellular transport of PTX-NCs was observed. These findings demonstrated that the rod-like nanocrystals not only enhanced the transcytosis of PTX compared with microparticles of raw drug materials but also changed the pathways of drug delivery. This study certainly provides insight for the oral absorption mechanism of nanocrystals of poorly soluble drugs.
研究领域:
药理学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 5
·4646
·
IF 5.6
Longkun Wang,Chunqian Zhao,Lu Lu,Honglei Jiang,Fengshan Wang,Xinke Zhang
Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As a key component in the standard treatment of TNBC, paclitaxel (PTX) effectively inhibits the growth and proliferation of tumor cells. However, the application of PTX in clinical treatment is limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, and side effects. To counter these problems, we constructed a novel PTX conjugate based on the peptide-drug conjugates (PDCs) strategy. In this PTX conjugate, a novel fused peptide TAR consisting of a tumor-targeting peptide, A7R, and a cell-penetrating peptide, TAT, is used to modify PTX. After modification, this conjugate is named PTX-SM-TAR, which is expected to improve the specificity and penetrability of PTX at the tumor site. Depending on hydrophilic TAR peptide and hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles and improve the water solubility of PTX. In terms of linkage, the acid- and esterase-sensitive ester bond was used as the linking bond, with which PTX-SM-TAR NPs could remain stable in the physiological environment, whereas PTX-SM-TAR NPs could be broken and PTX be released at the tumor site. A cell uptake assay showed that PTX-SM-TAR NPs were receptor-targeting and could mediate endocytosis by binding to NRP-1. The vascular barrier, transcellular migration, and tumor spheroids experiments showed that PTX-SM-TAR NPs exhibit great transvascular transport and tumor penetration ability. In vivo experiments, PTX-SM-TAR NPs showed higher antitumor effects than PTX. As a result, PTX-SM-TAR NPs may overcome the shortcomings of PTX and present a new transcytosable and targeted delivery system for PTX in TNBC treatment.Keywords:paclitaxel;peptide-drug conjugate;TAT peptide;A7R peptide;targeted delivery;anticancer therapy;transcytosis
研究领域:
药学
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Jinyu Liu,Yanhao Zhang,Chao Liu,Yuhao Jiang,Zihao Wang,Xinsong Li
Polypeptides are a highly promising carrier for delivering hydrophobic drugs, due to their excellent biocompatibility , non-toxicity, and non-immunogenicity. Herein, a redox and pH dual-responsive poly(ethylene glycol)-SS-b-polypeptide micelles encapsulated with disulfide bridged paclitaxel-pentadecanoic acid prodrug was developed for cancer chemotherapy . First of all, disulfide bridged paclitaxel-pentadecanoic acid prodrug (PTX-SS-COOH) and poly(ethylene glycol)-SS-b-polylysine-b-polyphenylalanine (mPEG-SS-b-PLys-b-PPhe, ESLP) were synthesized and confirmed via NMR, MS, FT-IR or GPC. After that, PTX-SS-COOH (PSH) embedded mPEG-SS-b-PLys-b-PPhe (ESLP/PSH) micelles were prepared by mixing method based on electrostatic interactions and hydrophobic forces. For comparison, mPEG-b-PLys-b-PPhe (ELP) was mixed with PTX-SS-COOH to generate another kind of micelles (ELP/PSH). The characterization of ESLP/PSH micelles through dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed a spherical structure with a diameter of approximately 170 nm . It is noteworthy that ESLP/PSH micelles displayed a high drug-loading rate of 22.84%, and excellent stability, which can be attributed to the specific interactions between the prodrug and copolymer . Drug release analysis demonstrated that the micelles exhibited a substantial release of PTX in the presence of GSH at pH 5.0, indicating a pH and redox dual responsiveness. In vivo pharmacokinetic study revealed the ESLP/PSH micelles had increased bioavailability and an extended circulation time. Ultimately, antitumor efficacy and systemic toxicity evaluation in 4 T1 tumor-bearing mice confirmed that ESLP/PSH micelles achieved the highest level of tumor growth inhibition (ca. 83%) and the lowest systemic toxicity in comparison with ELP/PSH micelles and commercialized Taxol®. Taken together, the dual responsive micelles represent a promising PTX formulation with potential clinical application in cancer chemotherapy.
研究领域:
药物递送
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Liu Zhanbiao,Chen Xuejun,Jin Qian,Li Min,Zhu Siqing,Zhang Yi,Zhi Defu,Zhao Yinan,Li Liqin,Zhang Shubiao
Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2023
·
IF 3.4
Zeyu Wang,Yuqi Chu,Xu Tao,Jianchao Li,Lihong Wang,Yuli Sang,Xiuli Lu,Lijiang Chen
To improve the aqueous solubility and oral bioavailability of paclitaxel (PTX), a biomimetic system for oral administration of PTX was efficiently developed as an outer membrane vesicle (OMVs) of sodium caseinate (CAS) modified zein nanoparticles (OMVs-Zein-CAS-PTX-NPs) by Escherichia coli. To verify their structure and properties, the designed nanostructures were thoroughly characterized using various characterization techniques. The results indicated that hydrogen bonds and van der Waals forces mainly drove the interaction between PTX and Zein, but the complex is unstable. The physicochemical stability of PTX-loaded zein nanoparticles was improved by the addition of CAS. The biological characteristics of biofilms are reproduced by nanoparticles cloaked with outer membrane vesicles. OMVs-Zein-CAS-PTX-NPs delayed the release of PTX under simulated gastric and intestinal fluids due to OMVs protection. OMVs-Zein-CAS-PTX-NPs exhibited remarkable antitumor ability in vitro and improved the bioavailability of oral administration of PTX in vivo. Therefore, OMVs cloaked in nanoparticles may be a suitable delivery vehicle to provide an efficient application prospect for the oral administration of PTX.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Hao Zhang,Chengyuan Xing,Binyuan Yan,Hanqi Lei,Yupeng Guan,Shiqiang Zhang,Yang Kang,Jun Pang
Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of β-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety in vivo, and enhanced the killing effect on prostate cancer.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Menglan Wang,Lewei Li,Lifang Tang,Zuowei Xiao,Hong Yang,Qian Luo,Shiyang Fu,Zehui Fan,Xiaojun Tao,Chunlian He,Xiong Wu
Chemoresistance remains a major barrier to the effective treatment of triple-negative breast cancer (TNBC). To enhance the targeting and chemosensitivity of paclitaxel (PTX) for TNBC treatment, we developed a dual-drug-loaded nanodelivery system (BBR@PTX NPs) using BI-PEG-PTX polymer as the carrier, with berberine (BBR) loaded at an optimal ratio (PTX:BBR =1:10) determined by synergistic toxicity assays. The BBR@PTX NPs in this study demonstrated loading efficiencies of 9.5% for PTX and 28.06% for BBR, with an average particle size of 130-150 nm and a uniform distribution. In in vitro cellular assays, BBR potentiates PTX, achieving synergistic anti-tumor efficacy. The BBR@PTX NP co-delivery system enhances bioavailability by evading macrophage phagocytosis and lysosomal capture. The ability to inhibit cell growth, metastasis, and induce apoptosis was significantly enhanced after the NPs were taken up by tumor cells. In vivo experiments demonstrated that the BBR@PTX NP nanomicellar system enhanced tumor targeting, anti-tumor activity, and biosafety compared to single-agent formulations. These findings establish an effective approach to develop high-performance, selective, and low-toxicity nanocellular aggregates for combined therapy of solid triple-negative breast cancer.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）